Prediction of tumor metastasis extracellular vesicles-treated platelet adhesion on a blood vessel chip

• Published in: Lab on a chip 2022-07, Vol.22 (14), p.2726-274
• Main Authors: Kim, Junyoung, Sunkara, Vijaya, Kim, Jungmin, Ro, Jooyoung, Kim, Chi-Ju, Clarissa, Elizabeth Maria, Jung, Sung Wook, Lee, Hee Jin, Cho, Yoon-Kyoung
• Format: Article
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/d2lc00364c

In preclinical and clinical studies, it has been demonstrated that tumor-educated platelets play a critical role in tumorigenesis, cancer development, and metastasis. Unlike the role of cancer-derived chemokines in platelet activation, the role of cancer-derived extracellular vesicles (EVs) has remained elusive. Here, we found that interleukin-8 (IL-8) in cancer-derived EVs contributed to platelet activation by increasing P-selectin expression and ligand affinity, resulting in increased platelet adhesion on the human vessel-mimicking microfluidic system. Furthermore, platelet adhesion levels on vessels treated with human plasma-derived EVs demonstrated good discrimination between breast cancer patients with metastasis and those without, with the area under the curve (AUC) value of 0.88. While EpCAM expression on EVs could detect the existence of a tumor (AUC = 0.89), it performed poorly in predicting metastasis (AUC = 0.42). We believe that these findings shed light on the role of the interaction between cancer-derived EVs and platelets in pre-metastatic niche formation and tumor metastasis, potentially leading to the development of platelet-tumor interaction-based novel diagnostic and therapeutic strategies. IL-8 of tumor-derived EVs activates platelets with elevated P-selectin expression and ligand affinity, thereby enhancing adhesion to vessel chips. The increased tumor adhesion on vessel chips can then be utilized to predict tumor metastasis.